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T Mazzone

Publications and source records attributed to T Mazzone.

62 records · Page 4Linked to original sources

Low density lipoprotein receptor activity in freshly isolated human blood monocytes and lymphocytes.

Circulating human monocytes and lymphocytes were isolated by counterflow and density gradient centrifugation. Binding and degradation of low density lipoprotein (LDL) occurred predominantly in monocytes and to a much lesser extent in lymphocytes. The findings were consistent with greater LDL receptor activity in freshly isolated monocytes than lymphocytes, in keeping with differences in other cell surface receptors between these two cell types. Therefore, when freshly isolated mixed mononuclear cells are used to study LDL receptor activity in vivo in humans, careful attention needs to be given to the proportions of monocytes and lymphocytes, or alternatively, relatively pure preparations of monocytes should be used.

Cell Separation↗

Apoprotein E biosynthesis in the cholesterol-fed guinea pig.

Apoprotein E biosynthesis was evaluated in the livers of guinea pigs fed chow, 1% cholesterol plus 5% corn oil, or 1% cholesterol plus 5% coconut oil for a period of 12 weeks. Hypercholesterolemia was induced by both experimental diets, although the coconut-oil diet resulted in higher levels. The ratios of free cholesterol/cholesterol ester and of free cholesterol/total phospholipid increased in the plasma of these animals. Peak lipid levels were mostly achieved by 8 weeks of diet. Both cholesterol and triglyceride were substantially increased in the liver of animals fed the experimental diets, while phospholipid content was unchanged. The amount of apoprotein E mRNA in the guinea pig livers was evaluated by cell free translation assays and by membrane hybridization. The livers of animals fed corn oil with cholesterol for 4 weeks or 8 weeks contained 2 to 2.5 more apoprotein E mRNA compared to the control livers. With the diet containing coconut oil with cholesterol, the hepatic apoprotein E mRNA increased somewhat later, so that by 8 weeks it was 1.7- to 1.9-fold higher than in the control animals. We conclude that high cholesterol diets, when fed as part of a high saturated or polyunsaturated fat diet, lead to increased hepatic apo E mRNA abundance. The relationship between the increased apo E mRNA levels and the previously described increases in apo E synthesis and circulating apo E levels is discussed.

Animals↗

A secretory product of human monocyte-derived macrophages stimulates low density lipoprotein receptor activity in arterial smooth muscle cells and skin fibroblasts.

The ability of macrophages to influence the metabolism of native low density lipoprotein by arterial smooth muscle cells was evaluated using cultured human monocyte-derived macrophages. Macrophage-conditioned medium stimulated the binding and degradation of low density lipoprotein by cultured arterial smooth muscle cells and skin fibroblasts. Sterol synthesis also was stimulated by macrophage-conditioned medium as was cholesterol esterification in the presence of high concentrations of low density lipoprotein. These findings suggest that macrophages secrete a factor that enhances the activity of the low density lipoprotein receptor. Low density lipoprotein degradation by arterial smooth muscle cells also was enhanced by macrophage-conditioned medium in the presence of high concentrations of low density lipoproteins in the medium. The macrophage factor that stimulates low density lipoprotein metabolism is stable to freezing, is inactivated by acid hydrolysis, tryptic digestion, and boiling, and is of large molecular weight (greater than 12,000 to 14,000 daltons). Modulation of arterial smooth muscle cell metabolism of low density lipoprotein by a macrophage secretory product may be of importance in the pathogenesis of atherosclerosis.

Binding Sites↗

Autoregulation of the modified low density lipoprotein receptor in human monocyte-derived macrophages.

Regulation of the macrophage receptor for modified low density lipoprotein (LDL) was evaluated using human monocyte-derived macrophages and acetyl LDL. Factors that regulate native LDL receptor activity in other cell types, such as the cholesterol content of the incubation medium, insulin, and platelet-derived growth factor had no effect on acetyl LDL degradation. Conditioned medium from mature macrophages significantly stimulated acetyl LDL degradation and enhanced cholesterol esterification by freshly isolated monocytes. Time course studies indicated that increasing time in culture was associated with increasing potency of the stimulating activity of macrophage-conditioned medium. These data suggest that a macrophage secretory product may be a prime modulator of modified LDL receptor activity on monocyte-macrophages, thus exerting an autocrine regulatory effect. The positive autoregulation of the human macrophage receptor for modified LDL could accelerate cellular cholesteryl ester accumulation and macrophage-derived foam cell formation.

Cell Differentiation↗

Modification of very low density lipoproteins leads to macrophage scavenger receptor uptake and cholesteryl ester deposition.

Chemically modified low density lipoproteins (LDL) are recognized by the macrophage scavenger receptor and can lead to substantial cholesteryl ester accumulation in cultured macrophages. Uptake of modified lipoproteins in vivo could contribute to foam cell formation during generation of the atherosclerotic plaque lesion. In the present study, modification of human pre-beta migrating very low density lipoprotein (VLDL) by acetylation led to recognition by the macrophage scavenger receptor as demonstrated in cross-competition experiments with acetylated LDL (ALDL). Recognition by this alternative binding site was associated with increased cholesterol delivery to human macrophages as assessed by suppression of LDL receptor activity, stimulation of cholesterol esterification rates, and accumulation of intracellular cholesteryl ester. Subfractionation of acetylated very low density lipoprotein (AVLDL) by ultracentrifugation in a discontinuous NaCl gradient demonstrated that AVLDL subfractions were equally effective in competing for 125I-ALDL uptake by macrophages when compared on the basis of particle number. These results suggest that modification of VLDL with subsequent recognition by the macrophage scavenger receptor may be a mechanism by which VLDL particles participate in macrophage cholesteryl ester overload.

Acetylation↗

Thyrotropin-secreting pituitary adenoma responsive to bromocriptine therapy.

OBJECTIVE: To describe a case of a thyrotropin-secreting pituitary adenoma that responded to bromocriptine therapy by suppression of thyrotropin and tumor shrinkage. METHODS: We present the clinical course, laboratory data, and radiographic findings in a 32-year-old woman with a thyrotropin-secreting pituitary adenoma before and after treatment with bromocriptine. RESULTS: The patient's pituitary tumor was detected after she had been treated with radioactive iodine for thyrotoxicosis presumed to be due to Graves' disease. After thyroid ablation, the thyrotropin levels could not be brought into the normal range, even while the patient was receiving supraphysiologic doses of orally administered levothyroxine. Magnetic resonance imaging of the pituitary, along with hormonal workup, confirmed the diagnosis of a thyrotropin-secreting pituitary adenoma. Because the tumor was not threatening vital structures and was considered incurable by operation, medical therapy was elected. A trial of bromocriptine was initiated at 15 mg/day and increased to 30 mg/day in three divided doses. Follow-up hormonal studies showed that thyrotropin levels declined into the suppressed range, and repeated magnetic resonance imaging scans showed substantial shrinkage of the pituitary lesion. CONCLUSION: Thyrotropin-secreting tumors may respond hormonally and structurally to bromocriptine therapy. In patients with such tumors, a trial of dopamine agonists at high dose may be considered before initiation of more invasive medical treatment.

Journal Article↗

[Postpartum depression].

From a review of the literature it emerges that postnatal depression is present in 10-15% of women during the first year after birth. Some studies have showed that a higher percentage of women with problems of depression commit infanticide compared to non-depressed women. A number of studies have been performed to identify the risk factors which may be used to predict postnatal depression during pregnancy; it is important that gynecologists recognise these factors in order to prevent the onset of this pathology during the postnatal period. Another aspect which emerges from the literature is that the absence of social rituals surrounding birth in the industrialised society, in which the transition role of the new mother is not always recognised, may be an important factor in the etiology of postnatal depression.

Depression↗